Migraine and Cluster Headaches

January 29, 2018

Amgen reported positive results from the Phase IIIb LIBERTY study assessing the efficacy and safety of Aimovig (erenumab) 140mg in patients with episodic migraine who had experienced two to four previous preventive treatment failures, due to lack of efficacy or intolerable side effects. The multicenter, randomized 12-week, double-blind, placebo-controlled study enrolled 246 participants. The study includes an ongoing 52-week open-label extension study. The study met its primary endpoint, with significantly more patients taking Aimovig experiencing at least a 50 percent reduction from baseline in their monthly migraine days as compared to placebo. LIBERTY also met all secondary endpoints, including reduction of monthly migraine days, reduction in days needing acute (rescue) medication, improvement in scores on the Migraine Physical Function Impact Diary (MPFID) tool, and 75 percent and 100 percent responder rates (number of patients experiencing at least a 75 percent or 100 percent reduction in monthly migraine days compared to placebo). The safety data are consistent with previous studies of Aimovig to date. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of May 17, 2018.

January 15, 2018

Alder BioPharmaceuticals announced that eptinezumab, its lead investigational product candidate for migraine prevention targeting calcitonin gene-related peptide (CGRP), met the primary endpoint in its pivotal Phase III PROMISE 2 clinical trial with very high statistical significance vs. placebo (p<0.0001) for both dose levels tested in the trial following a single quarterly infusion. In addition, eptinezumab met all key secondary endpoints with very high statistical significance vs. placebo including prevention beginning Day One (p<0.0001) and 50 percent (p<0.0001) and 75 percent (p<0.0001) responder rates month one through month three. Furthermore, 15 percent of eptinezumab patients had no migraines (i.e., 100 percent response) for a full three months (p<0.0001 unadjusted). Safety and tolerability were similar to previously reported eptinezumab studies. The observed safety profile in this study, to date, is consistent with previously reported eptinezumab studies. Adverse event rates among eptinezumab-treated subjects were similar to placebo-treated subjects. Commonly reported adverse events for eptinezumab, occurring at an incidence of 2.0 percent or greater, were nasopharyngitis (common cold) (6.3 percent), upper respiratory infection (4.0 percent), nausea (3.4 percent) and urinary tract infection (3.1 percent), arthralgia (joint pain) (2.3 percent), dizziness (2.6 percent), anxiety (2.0 percent) and fatigue (2.0 percent). If approved by the FDA, eptinezumab will be the first-to-market migraine prevention infusion therapy, with 100 percent of the treatment dose available upon administration.

September 18, 2017

Eli Lilly reported results of a phase III study of galcanezumab for migraine. In the 12-month, open-label study, 270 patients were randomized to treatment with galcanezumab 120mg or galcanezumab 240mg. Galcanezumab was associated with a statistically significant reduction in the number of monthly migraine headache days with both doses (5.6 days for 120mg and 6.5 days for 240mg, p<0.001 for both dosing groups). Notably, there was no clinically meaningful difference in the rate of adverse events between galcanezumab 120mg and 240mg dosing groups. The most commonly reported adverse events (≥10%) in both dosing groups included injection site pain, nasopharyngitis and upper respiratory tract infection. Serious adverse events were reported by three patients in the 120mg dosing group and seven patients in the 240mg group. Lilly plans to submit a Biologics License Application (BLA) to the FDA for galcanezumab in the second half of 2017, followed by submissions to other regulatory agencies around the world.

July 3, 2017

Alder BioPharmaceuticals issued results of a phase III study of eptinezumab for frequent episodic migraine. PROMISE 1 was a double-blind, randomized, placebo-controlled study evaluating eptinezumab (300mg, 100mg or 30mg) administered by intravenous infusion once every 12 weeks through week 24. PROMISE 1 met the primary endpoint: highly statistically significant reductions in monthly migraine days. Significant Day 1 clinical benefit was a ≥50% reduction in the proportion of patients experiencing a migraine on Day 1 post-dose. There were significant 75% responses at all key time points: ~1/3 of patients achieved a ≥75% reduction in migraine days through four and 12 weeks. An average of one in five patients had 100% response: no migraines in any given month, months one through six. Enrollment is on track for PROMISE 2, a second pivotal phase III study that focuses on chronic migraine, and the company is on track to submit a BLA with the FDA in 2018.

June 19, 2017

Eli Lilly released results from three
phase III studies of galcanezumab for the prevention of episodic and chronic migraine. In the EVOLVE-1 and EVOLVE-2 studies,
over the six-month treatment period, patients with episodic migraine treated
with galcanezumab 120mg and 240mg doses experienced a statistically significantly greater decrease in the average number of monthly migraine headache days compared to patients treated with placebo, with statistically significant improvements observed at each month starting at one month of treatment. A statistically significantly greater percentage of patients treated with both doses of galcanezumab achieved at least a 50%, 75% and 100% reduction in the number of migraine headache days compared to placebo over the six-month treatment period, in both studies after multiplicity adjustment. In the REGAIN study, over the three-month treatment period, patients with chronic migraine treated with galcanezumab 120mg and 240mg doses experienced a statistically significantly greater decrease in the average number of monthly migraine headache days compared to patients treated with placebo. Statistically significant improvements for both doses of galcanezumab were observed at each month starting at one month of treatment. A statistically significantly greater percentage of patients also achieved at least a 50% reduction in the number of migraine headache days compared to placebo over the three-month treatment period (27.6% for 120mg and 27.5% for 240mg compared to 15.4% for placebo, p<0.001 for both dosing groups) after multiplicity adjustment. Based on these results, Lilly will submit a Biologics License Application to the FDA for galcanezumab in the second half of 2017, followed by submissions to other regulatory agencies around the world.

June 5, 2017

Teva Pharmaceutical Industries announced positive results from a phase III HALO study of fremanezumab, an investigational treatment for the prevention of migraine. In the chronic migraine (CM) study, patients treated with fremanezumab experienced statistically significant reduction in the number of monthly headache days of at least moderate severity vs. placebo (-2.5 days) during the 12 week period after first dose, for both monthly (-4.6 days p<0.0001) and quarterly (-4.3 days p<0.0001) dosing regimens. Similar to the Phase II trials, both patients that were on monotherapy and stable doses of prophylactic medications were included in the trial. In addition, patients treated with fremanezumab experienced significant improvement compared to placebo on all secondary endpoints for both monthly and quarterly dosing regimens, including: response rate, onset of efficacy, efficacy as monotherapy, and disability. The results were positive, and of 13 hierarchical comparisons, p was <0.0001 in 12 of them, being 0.0004 in the remaining. The most commonly-reported adverse event in the study was injection site pain, with similar rates in the placebo and active groups. Based on these results, Teva plans to submit a Biologics License Application to the FDA for fremanezumab later this year.

July 6, 2015

Avanir Pharmaceuticals issued results of
a phase IIIb trial comparing AVP-825 22mg to
sumatriptan 100mg tablets for the treatment
of acute migraine. The study is a multicenter,
randomized, double-blind, double-dummy
crossover study in which migraine sufferers
were treated with either 22mg of AVP-825 and
placebo or Breath Powered device-delivered
placebo and 100mg sumatriptan tablet. Study
participants were instructed to treat up to five
migraine attacks in each treatment period of
up to 12 weeks. Migraine pain and presence
of migraine associated symptoms of phonophobia,
photophobia and nausea/vomiting
were assessed immediately before dosing and
at 10, 15, 30, 45, 60, 90, 120 minutes and at 24
and 48 hours after administration. 275 participants
and 1,531 migraines were assessed
during the study. Results showed that patients
treated with AVP-825 achieved pain relief and
pain freedom in significantly more migraine
attacks at all time points from 15-90 minutes
post-dose compared to sumatriptan tablets.
AVP-825 and sumatriptan tablets achieved
sustained pain relief and pain freedom at 24
and 48 hours in a similar number of attacks. In
addition, AVP-825 treated patients experienced
early resolution of all migraine-associated
symptoms of nausea, sensitivity to sound
and to light in more attacks compared with
sumatriptan tablets. An NDA for AVP-825 has
been accepted and currently is under review
by the FDA with a PDUFA goal date of Nov. 6.

June 16, 2014

OptiNose reported results of a trial
comparing AVP-825 to sumatriptan
tablets for migraine pain during the first
30 minutes after treatment. The multi-center,
randomized, double-blind, double-dummy
crossover, multi-attack study enrolled
275 migraine sufferers and treated a
total of 1,531 acute migraines with either
the only dose of AVP-825 (22mg) plus a
placebo tablet or with a placebo delivered
with an OptiNose Bi-Directional Breath
Powered device, plus a high dose (100mg)
sumatriptan tablet. The trial showed with
AVP-825 treatment, early reduction in pain
was achieved in more headaches than
with oral sumatriptan. The primary endpoint
showed during the first 30 minutes,
headache pain intensity was statistically
significantly lower with AVP-825 treatment
(p<0.0001). In addition, the trial achieved
statistical significance for relevant secondary
measures of Pain Relief and Pain
Freedom as early as 15 minutes and at all of
the following early time points measured
(30, 45, 60, 90) before 120 minutes. Less
than 2% of subjects experienced an adverse
event leading to treatment discontinuation
with use of either medication and there
were no serious adverse events. An NDA for
AVP-825 was filed earlier this year, and the
Prescription Drug User Fee Act (PDUFA) V
goal date is Nov. 26.

October 25, 2010

NuPathe issued positive results from a phase III trial of Zelrix for the treatment of migraine. This 12 month open-label safety trial, NP101-008, enrolled 183 subjects who applied at least one Zelrix patch. Efficacy response was evaluated two hours after application of Zelrix for the treatment of a moderate to severe migraine. Results showed the following: headache pain relief within two hours for 58% of migraines treated; headache pain freedom within two hours for 24% of migraines treated; freedom from nausea within two hours for 79% of migraines treated and rescue medication used in only 19% of migraines treated. Zelrix was well tolerated. The most common adverse events were application site itching, application site pain and application site hypersensitivity.

September 21, 2009

MAP Pharmaceuticals reported positive results from a phase III trial of Levadex for the treatment of migraine headaches. This multi-center trial, FREEDOM-301, consisted of a randomized, double blind, placebo-controlled portion, to evaluate the efficacy and safety of Levadex in treating a single acute attack of migraine in 792 subjects, followed by a 12-month open-label safety assessment. The co-primary endpoints were improvement in pain relief and freedom from nausea, photophobia and phonophobia at two hours. All four co-primary endpoints were reached with significance at two hours: pain relief (p<0.0001); phonophobia free (p<0.0001); photophobia free (p<0.0001) and nausea free (p≡0.02). In addition, Levadex showed improvement over placebo in pain relief at 10 minutes (p≡0.16) and time to pain relief at 30 minutes (p≡0.03); sustained pain relief from two to 24 hours (44% vs. 20%; p<0.0001); sustained pain relief from two to 48 hours (36% vs. 17%; p<0.0001) and sustained pain free from two to 24 hours (23% vs. 7%) and from two to 48 hours (18% vs. 6%) (p<0.0001 for both timepoints).

May 18, 2009

Addex issued positive results from a phase IIa trial of ADX10059 for the treatment of migraine headaches. This multicenter, randomized, double-blind, placebo-controlled parallel study enrolled 129 subjects diagnosed with acute moderate to severe migraine who received a single dose of ADX10059 or placebo. Significantly more subjects in the ADX10059 treatment arm were pain-free two hours after dosing compared to placebo (16.7% versus 4.7%, respectively; p≡0.039). In addition, there were trends to superiority for ADX10059 over placebo for migraine pain improvement (mild or no pain) at all time points up to two hours post-dosing. A lack of functional impairment two hours after taking the drug also trended towards superiority in the ADX10059 treatment arm, although this was not significant, (8.5% versus 3.3%).

September 22, 2008

NeurAxon issued mixed results from a phase II trial of NXN-188 for the treatment of migraine headache. This randomized, multi-center, double-blind, placebo-controlled parallel-group study enrolled 60 subjects experiencing migraine. The subjects received one of three doses of NXN-188 or placebo. The primary endpoint was not reached. In the overall population, the subjects receiving NXN-188 experienced a 15% greater effect than placebo in migraine pain relief at two hours. In the secondary analysis, NXN-188 showed a 32% and 35% greater effect than placebo at four hours and six hours, respectively. However, a post-hoc analysis of a group of subjects experiencing migraine with aura showed statistically significantly sustained pain relief for up to 24 hours, without rebound headache, when compared to placebo. This response was observed in 22%, 48% and 68% of subjects at two, four and six hours, respectively. NXN-188 was well tolerated and there were no reported serious adverse events. Based on the results, NeurAxon is planning a phase II trial specifically for the treatment of migraine with aura.

September 15, 2008

Merck reported positive results from a phase III trial of telcagepant for the treatment of migraine headaches. This randomized, placebo-controlled study enrolled 1,703 subjects across several international sites. The subjects received placebo or telcagepant at doses of either 300 mg, 150 mg or 50 mg. Five primary endpoints were analyzed at two hours post-dose: pain, pain relief, absence of photophobia, absence of phonophobia and absence of nausea. The treatment effect of the 300 mg and 150 mg doses of telcagepant was significantly greater than placebo for all five primary endpoints (p<0.001 for both doses on all endpoints, except p<0.050 for 150 mg dose on phonophobia). Secondary endpoints were reached as well, including two to 24 hours sustained pain freedom, total migraine freedom from two to 24 hours post-dose, and total migraine freedom at two hours post-dose. Based on the results, Merck plans to file an NDA with the FDA in 2009.

NeurAxon issued mixed results from a phase II trial of NXN-188 for the treatment of migraine headache. This randomized, multi-center, double-blind, placebo-controlled parallel-group study enrolled 60 subjects experiencing migraine. The subjects received one of three doses of NXN-188 or placebo. The primary endpoint was not reached. In the overall population, the subjects receiving NXN-188 experienced a 15% greater effect than placebo in migraine pain relief at two hours. In the secondary analysis, NXN-188 showed a 32% and 35% greater effect than placebo at four hours and six hours, respectively. However, a post-hoc analysis of a group of subjects experiencing migraine with aura showed statistically significantly sustained pain relief for up to 24 hours, without rebound headache, when compared to placebo. This response was observed in 22%, 48% and 68% of subjects at two, four and six hours, respectively. NXN-188 was well tolerated and there were no reported serious adverse events. Based on the results, NeurAxon is planning a phase II trial specifically for the treatment of migraine with aura.

July 14, 2008

Merck positive results from a phase III trial of telcagepant for the treatment of migraine headaches. This randomized, double-blind, placebo controlled trial enrolled 1,380 adult subjects who had experienced a single moderate or severe migraine attack. The subjects received either telcagepant (as a gel capsule) at doses of either 150 mg or 300 mg or zolmitriptan 5 mg or placebo. Five primary endpoints were analyzed at two hours post-dose. The 300 mg dose of telcagepant was significantly greater than placebo for all five primary endpoints in the study (p=<0.01) and comparable to zolmitriptan. The data for each of the endpoints is as follows: two-hour pain relief: 55% of subjects who received telcagepant reported their pain had been reduced at two hours compared to 56% for zolmitriptan and 28% for placebo; two-hour pain freedom: 27% of subjects in the telcagepant arm reported being pain free at two hours compared to 31% for zolmitriptan and 10% for placebo; absence of phonophobia: 58% of subjects who received telcagepant reported they were not experiencing sensitivity to noise at two hours compared to 55% for zolmitriptan and 37% for placebo; absence of photophobia: 51% of subjects in the telcagepant arm reported they were not experiencing sensitivity to light compared to 50% for zolmitriptan and 29% for placebo; and absence of nausea was reported in 65% of subjects who received telcagepant, 71% for zolmitriptan and 55% for placebo. All secondary endpoints were reached as well. The rates of overall adverse events observed in the telcagepant 300 mg arm were similar to placebo and lower than the zolmitriptan arm (37%, 32% and 51%, respectively). Merck plans to file an NDA with the FDA in 2009.

October 29, 2007

Amicus reported positive results from two phase I trials of AT2220 for the treatment of Pompe Disease. These double-blind, placebo-controlled, dose escalation studies were designed to evaluate the safety, tolerability and pharmacokinetics of AT2220. In a single ascending dose study, 32 subjects received oral doses of AT2220 (50, 150, 300, or 600 mg) or placebo. In a multiple ascending dose study, 24 subjects received oral doses of AT2220 (50, 150, or 450 mg/day) or placebo for 7 days. Treatment was determined to be safe and well tolerated at all doses tested. In the multiple ascending dose study all possible drug-related adverse events were mild and resolved spontaneously. AT2220 was orally bioavailable with a plasma half-life of 4 to 5 hours. Based on the results, Amicus plans to initiate phase II trials early in 2008.

MediciNova issued negative results from a phase IIa trial of MN-305 for the treatment of insomnia. This randomized, double-blind, placebo-controlled, four-period crossover dose-response study enrolled 90 subjects with primary insomnia in the US. Each subject received three doses of MN-305 (1 mg, 3 mg and 6 mg) and placebo, administered orally approximately 60 minutes before bedtime, for seven consecutive nights. The primary endpoint, statistical significance in the reduction of Wake (time) After Sleep Onset (WASO), was not met. Treatment was well tolerated at all doses tested. Based on the results, MediciNova plans to discontinue the development of MN-305 for insomnia and focus on other potential indications.

TorreyPines reported positive results from a phase IIb trial of tezampanel for the treatment of migraine headaches. This randomized, double-blind, placebo-controlled, parallel-group study enrolled 306 subjects in the US. The subjects were equally randomized to one of four treatment arms: tezampanel 40 mg, 70 mg, or 100 mg or placebo administered as a single, subcutaneous dose. The primary endpoint was headache pain response at two hours post-dose. Statistical significance was observed in the 40 mg arm, with improvement in headache response reported in 78.2% of the subjects versus 58.7% in the placebo arm (p=0.033). This response was sustained through 24 hours post-dose. Statistical significance was not reached in the 70 mg arm (63.5%; p=0.890) or the 100 mg arm (57.1%; p=0.890). The 40 mg arm achieved the secondary endpoints as well, with improvements over placebo in nausea (p=0.014), photophobia (p=0.056) and phonophobia (p=0.227). Treatment was well tolerated, with no reports of serious adverse events. Based on the results, TorreyPines plans to commence phase III trials in 2008.

August 20, 2007

Cephalon issued positive results from a phase III trial of Fentora for the treatment of break-through pain associated with chronic non-cancer pain conditions. This double-blind, placebo-controlled, variable dose trial enrolled 148 opioid-tolerant subjects who received treatment for 12 weeks. The primary endpoint was the Sum of Pain Intensity Differences from five to 60 minutes (SPID) after 12 weeks of treatment. Subjects treated with Fentora showed a statistically significant improvement in the primary endpoint compared to placebo (p<0.0001). Treatment was well tolerated, with no reported unexpected adverse events. Based on the results, Cephalon plans to file a sNDA with the FDA in Q4 of 2007.

NeurAxon released positive results from a phase I trial of NXN-188 for the treatment of migraine headaches. This randomized, double-blind, placebo-controlled dose escalation study was designed to evaluate the safety and pharmacokinetics of the drug. Subjects received nine single oral dose levels of either NXN-188 or placebo. Treatment was determined to be well tolerated at all dose levels, with no reported adverse events. Based on the results, NeurAxon plans to initiate phase IIa trials in Q3 of 2007.

June 18, 2007

Merck announced positive results from a phase II trial of MK-0974 for the treatment of migraine headaches. This randomized, double-blind, placebo- and active-controlled dose-ranging trial enrolled 420 subjects. Subjects received MK-0974 administered orally at doses of 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, or 600 mg, or rizatriptan 10 mg, or placebo. The first stage of the study evaluated doses of MK-0974 with rizatriptan and placebo. When a predetermined number of migraine attacks were treated, an interim efficacy analysis was conducted resulting in dropping the four lowest doses of MK-0974. The second stage of the study continued with the randomization of subjects to MK-0974 300 mg, 400 mg or 600 mg or to rizatriptan 10 mg or placebo. Statistical significance was seen in the primary endpoint of overall efficacy of MK-0974 in relieving pain two hours after dosing when compared to placebo (p=0.015). The secondary endpoint, overall treatment effect compared to placebo, also reached statistical significance ((p<0.001). Treatment was well tolerated, with no reported adverse events. Based on the results, Merck plans to move forward with the development of MK-0974.

April 30, 2007

Addex issued positive results from a phase IIa trial of ADX10059 for the treatment of migraine headaches. This double-blind, placebo-controlled comparison trial enrolled 129 subjects in the United Kingdom and Germany. Subjects received a single dose of ADX10059 or placebo to treat a single moderate or severe (IHS Grade 2 or 3) migraine, in an outpatient setting. The primary endpoint was the proportion of subjects pain-free (IHS 0) two hours after dosing. This endpoint reached statistical significance, with 16.1% of the subjects taking ADX10059 pain-free compared to 4.5% of those taking placebo (p = 0.039). Improvement in migraine pain could be seen from 1 hour after dosing, with the compound being numerically superior to placebo at 1.0 and 1.5 hours post-dose. In addition, there were trends to superiority for ADX10059 over placebo for migraine pain improvement (mild or no pain) at all time points up to two hours post-dosing. Based on the results Addex plans to initiate phase IIb trials shortly.

Amarin reported negative results from two phase III trials of Miraxion for the treatment of Huntington's disease. These randomized, double-blind, placebo-controlled trials enrolled 600 subjects who received Miraxion 2g (1g twice daily) or placebo for six months. The primary endpoint was a change in the Total Motor Score 4 (TMS-4) component of the Unified Huntington's Disease Rating Scale (UHDRS). Secondary endpoints included cognition, behavioral and Total Functional Capacity outcomes. Data showed no statistically significant difference in either study between Miraxion and placebo with regard to the primary and secondary endpoints. Amarin plans to fully evaluate the data in order to determine a future course of action.

UCB announced positive top-line results from a phase III trial of Keppra for adjunctive therapy in the treatment of partial onset seizures in children. This double-blind, randomized, placebo-controlled study enrolled 116 children aged one month to four years. Subjects received Keppra (20-50 mg/kg/day) or placebo for five days. The primary endpoint was efficacy based on a 48 hour video EEG performed at baseline and at the end of the evaluation period. Results revealed 43.1% of Keppra-treated subjects experienced at least a 50% reduction in seizure frequency during the evaluation period compared with 19.6% of placebo-treated subjects. Treatment was generally well tolerated, with the most common adverse events somnolence and irritability. Based on the results UCB plans to file a sNDA with the FDA for Keppra as therapy in this population.

April 2, 2007

Aeolus announced positive results from a phase I trial of AEOL10150 for the treatment of Amyotrophic Lateral Sclerosis (ALS). Thisdouble-blind, randomized, placebo-controlled trial enrolled 18 subjects whowere placed into three groups of six subjects, with four receiving AEOL 10150and two receiving placebo. Each subject in the first two cohorts receivedsubcutaneous (SC) injections of AEOL 10150 or placebo for six days, followed bya single SC injection on the seventh day, for a total of 13 injections. In thefirst cohort, each injection was 40 mg and in the second cohort each injectionwas 60 mg. In the third cohort subjects received a daily dose of 2 mg/kgdelivered by osmotic infusion pump over 24 hours for 6.5 days. Treatment wasgenerally well tolerated, with injection/infusion site reactions the mostcommon adverse event. Pharmacokinetic analyses showed a dose related increasein plasma concentrations between 40 and 60 mg bid. The continuous infusion ofAEOL 10150 2 mg/kg/day resulted in lower, but sustained, plasma levels ofapproximately 1,500 ng/ml. The maximum tolerated dose was not reached. Based onthe results Aeolus plans to move forward with the development of AEOL 10150.

Alexza released positive results from a phase IIb trial of AZ-001for the treatment of migraine headaches. This randomized, double blind,placebo-controlled trial enrolled 400 migraine subjects with and without aura.Subjects received one of three doses of AZ-001 (5 mg, 7. 5 mg or 10 mg) orplacebo. The primary endpoint, pain relief at 2-hours post-dose using theInternational Headache Society (HIS) 4-point scale, was met for all three dosesof AZ-001 compared to placebo. Statistical significance in pain response wasobserved in 66% of subjects at the 10 mg dose (p=0.0013), 63.7% of those at the7.5 mg dose (p=0.0046) and 60.2% of subjects at the 5 mg dose (p=0. 0076),compared to 40.8% of subjects receiving placebo. Secondary endpoints were metas well in pain-free response at 2 hours for AZ-001 compared to placebo.Statistical significance was observed in the 10 mg AZ-001 group, with 35% ofsubjects achieving pain-free status (p=0.0019) and in the 7. 5 mg dose group,with 29.7% of the subjects achieving pain-free status (p=0.0226) versus 15. 3%of those on placebo. Statistical significance was also seen in sustained painfree response for up to 24 hours in the 10 mg group (30.1% of the subjects) and7.5 mg group (23.1% of the subjects) versus the placebo group (10. 2% of thesubjects). In addition, AZ-001 had a rapid onset of pain relief. At 30 minutes,all three doses of AZ-001 showed statistically significant pain response,compared to placebo; 10 mg (p=0.0056), 7.5 mg (p=0.0003) and 5 mg (p=0. 0056).Based on the results, Alexza plans to move forward with the development ofAZ-001.

MediciNova reported positive results from a phase II trial ofMN-166 for the treatment of multiple sclerosis. This randomized, double-blind,placebo-controlled trial enrolled 297 subjects who received placebo or MN-166in a 30 or 60 mg per day dose, for 12 months. The primary endpoint, efficacybased on the evaluation of the cumulative number of active(gadolinium-enhancing (T1) and non-enhancing new/enlarging (T2)) cranial MRIlesions, was not met. No reduction in active lesions was observed. However,when compared to the placebo group, a significantly higher proportion of thesubjects who received 60 mg per day of MN-166 remained relapse free over 12months (p=0.03) and had a significant increase in the time to first relapse(p=0.04). In addition, a significant reduction in brain volume loss wasobserved in the 60 mg dose group when compared to placebo (p=0. 04). Based onthe results, MediciNova plans to continue the trial beyond the first year oftreatment in order to gather and evaluate data to support a phase III trial.

January 31, 2005

MedPointe Pharmaceuticals has reported results from a long-term phase III safety and tolerability study of the approved drug Zomig nasal spray, for the treatment of migraine. Data from study patients, accounting for 20,717 migraine attacks, found that the drug was safe and largely well tolerated, with serious adverse events occurring in only 0.1% of attacks, and only three such events were considered drug-related (nausea, vertigo and angina pectoris). Minor adverse events included unusual taste (19.0%) and paresthesia (6.8%), but these were generally tolerated, leading to trial withdrawals in only 0.4% and 0.6% of patients, respectively. Furthermore, adverse event incidence declined over time, from 43.4% of attacks from 0-90 days to 30.7% at 361 days or later. Secondary efficacy endpoints were also met, with 53.8% of attacks resolving within 2 hours. This open-label, noncomparative, multicenter trial enrolled 538 subjects with a history of recurrent migraines; subjects received treatment with Zomig during migraine attacks of any severity for 1 year.

Winston Laboratories has issued positive results of a phase III study of their topical civamide cream 0.075%, for the treatment of pain in osteoarthritis. Data from the trial met their primary efficacy endpoints, with significant improvements noted in symptom severity scores on the Pain and Physical Function subscales of the Western Ontario McMaster Osteoarthritis Index, and Subject Global Evaluation (a measure of patient satisfaction with treatment) after 12 weeks (p<0.05). The data also met secondary pharmacokinetic and safety/tolerability endpoints, with no detectable systemic absorption, no serious adverse events, and a transient, mostly mild-to-moderate burning sensation at the application site which decreased in frequency as treatment progressed (<9% by week 3). This double-blind, vehicle-controlled, parallel arm study enrolled 695 patients with moderate-to- severe osteoarthritis pain that was being treated with, but not sufficiently controlled by, oral NSAID or COX-2 therapy. Subjects were randomized to receive either the experimental 0.075% cream or a vehicle cream containing only a small amount (0.01%) of civamide via topical application for 12 weeks.

October 18, 2004

Hemispherx Biopharma presented expanded data from their phase III study of Ampligen, for the treatment of chronic fatigue syndrome (CFS), at the 7th International Conference for CFS in Madison, Wisconsin. The data, which covered subjects in the intent-to-treat population, demonstrated that subjects receiving the drug experienced symptom relief, with a significant improvement in treadmill exercise tolerance (p=0.037) compared with placebo; this improvement was more than twice the level required to achieve medical significance. Secondary safety endpoints were also satisfied, with no significant difference in serious adverse events, missed dosages or dropouts between Ampligen and placebo groups. The double-blind, placebo-controlled study randomized 234 patients with severe/debilitating CFS across 12 US sites to receive twice weekly doses of either 400 mg. Ampligen or placebo for 40 weeks. Following these results, Hemispherx announced that they were preparing for the filing of a NDA for Ampligen; if approved, the drug would be the first drug indicated for the treatment of CFS.

NPS Pharmaceuticals reported negative results of a proof-of-concept clinical trial of NPS 1776 (isovaleramide), for the treatment of acute migraine headaches. The study failed to meet its primary endpoint, a significant reduction in acute headache pain two hours after administration compared with placebo. NPS attributed this failure to a higher-than expected placebo effect: 56% of subjects receiving placebo achieved primary response, compared with 60% of subjects receiving the higher dose of the drug and 64% of subjects receiving the lower dose. Secondary safety endpoints were met, with no serious adverse events and no minor events occurring more frequently with the drug than placebo. The double-blind, placebo-controlled study randomized 189 patients with moderate-to-severe migraine pain to receive one of two doses of the drug or placebo. NPS announced that they planned to continue investigation of the drug in other indications, but did not report the intention to continue pursuing the drug for migraine.

Prana Biotechnology announced the results of an open-label extension of a phase II study of PBT-1 (clioquinol), a copper-zinc attenuator/amyloid-beta aggregation inhibitor for the treatment of Alzheimer&#8217;s disease (AD). Data from the study confirmed the positive results achieved in the original trial: subjects experienced a mean decline of 8 points on the ADAS-cog scale, a standardized diagnostic scale for cognitive performance in AD, compared with a literature-established expected decline of 18 points. The drug was also found to be safe and well tolerated, with no significant increase in adverse events over untreated subjects. This 48-week open-label extension to the 36-week double-blind, placebo-controlled phase II CQAD study enrolled 18 of the original participants, 9 of whom completed treatment. Prana announced that they were continuing to evaluate the study data, in preparation for advancing the drug into further clinical studies.

October 13, 2003

GlaxoSmithKline reported positive results from a post-marketing study investigating Imitrex (sumatriptan succinate) for the treatment of menstrual migraines. Results showed that more than half of the subjects treated with Imitrex (61% and 51% at 100 mg & 50 mg respectively) experienced more complete relief of migraine pain two hours after treatment than with placebo (29%). Data also showed that 51% and 47% of subjects, at 100 mg and 50 mg were free of migraine pain and associated symptoms such as nausea, vomiting, and sensitivity to light and sound versus 25% with placebo. The randomized, double-blind, placebo-controlled study enrolled 349 female subjects with at least a one-year history of migraine and a six-month history of regularly occurring menstrually associated migraines. Subjects were randomized to receive Imitrex 50 mg, 100 mg, or placebo. Pain was rated by subjects on a standard four-point scale. Results were reported in the October issue of Obstetrics & Gynecology.<

April 14, 2003

Ortho-McNeil Pharmaceutical reported positive results from a phase III trial investigating Topamax (topiramate), an approved seizure drug for the new indication of migraine headaches. Results showed that treatment with Topamax (100/200 mg) demonstrated significant improvements in mean monthly migraine frequency. Data revealed that the average number of migraines per month was at least cut in half for 49% of subjects treated with Topamax (100 mg), 47% of subjects taking 200 mg and 39% of subjects taking 50 mg. The 26-week, multi-center, randomized, placebo-controlled study enrolled 483 subjects with frequent migraine headaches. The drug was found safe and generally well tolerated with no unexpected adverse events attributed to treatment. Subjects were administered Topamax or placebo at doses of 50, 100 or 200 mg/day.

January 27, 2003

Nastech Pharmaceutical reported positive results from a Phase I trial investigating sumatriptan, a selective serotonin receptor agonist for the treatment of migraine headaches. Results showed a significantly higher peak concentration and nearly double the amount of drug maintained in the bloodstream compared to the marketed product Imitrex. Sumatriptan (5mg nasal) showed a mean time to half-maximum concentration of 14 minutes compared to 45 minutes for Imitrex (5mg nasal). No serious adverse events were reported and non-serious adverse events were mild. In addition, no nasal irritation was observed during the trial. The non-blinded, crossover study enrolled 12 healthy male subjects and was designed to test the safety, pharmacokinetic, and tolerance of sumatriptan compared to the marketed drug Imitrex.

July 29, 2002

Preliminary results from the first phase III clinical study of MT 300 for the treatment of migraines indicated that the sustained response rate for subjects receiving MT 300 was 37%, which was statistically greater than the 19% sustained response rate demonstrated by subjects receiving placebo. Sustained response was defined as subjects achieving pain relief within 2 hours of dosing and neither relapsing nor using rescue medication for the following 22 hours. MT 300 also provided pain relief in significantly more patients at 2 and 4 hours compared to placebo. The most commonly reported adverse event was injection site reaction. This double-blind, placebo-controlled study was conducted at 36 U.S. sites in 619 subjects with acute migraine. MT 300 is being developed by Pozen.

April 29, 2002

Positive results were reported from a placebo-controlled study of AstraZeneca's Zomig (zolmitriptan) in women with migraine associated with menses. Subjects treated severe migraine attacks with 5.0 mg Zomig tablets, moderate attacks with 2.5 mg and mild attacks with 1.25 mg. At 30 minutes, 18% of subjects treated with Zomig achieved headache response (reduction from severe/mild pain to mild/none), compared to 14% of placebo-treated subjects. Additionally, headache response was 33% and 48% for the Zomig group, versus 23% and 27% for the placebo group, at one and two hours, respectively.